Local hyperthyroidism promotes pancreatic acinar cell proliferation during acute pancreatitis

[helvella]

Although we so often see discussion about the need for T3, we see precious little about its precise effect. This paper identifies some quite fine detail in the context of the pancreas.

Of course, if adequate T3 is required, what does that imply of the impact of inadequate T3?

J Pathol. 2019 Feb 4. doi: 10.1002/path.5247. [Epub ahead of print]

Local hyperthyroidism promotes pancreatic acinar cell proliferation during acute pancreatitis.

Malagola E1, Chen R1, Bombardo M1, Saponara E1, Dentice M2, Salvatore D2, Reding T1, Myers S3, Hills AP3, Graf R1,4, Sonda S1,4,3.

Author information

1 Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland.

2 Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

3 School of Health Sciences, College of Health and Medicine, University of Tasmania, Australia.

4 Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland.

Abstract

Proliferation of pancreatic acinar cells is a critical process in the pathophysiology of pancreatic diseases, because limited or defective proliferation is associated with organ dysfunction and patient morbidity. In this context, elucidating the signalling pathways that trigger and sustain acinar proliferation is pivotal to develop therapeutic interventions promoting the regenerative process of the organ. In this study we used genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones to elucidate their role in acinar proliferation following caerulein-mediated acute pancreatitis in mice. In addition, molecular mechanisms mediating the effects of thyroid hormones were identified by genetic and pharmacological inactivation of selected signalling pathways. In this study we demonstrated that levels of the thyroid hormone 3,3',5-triodo-L-thyronine (T3) transiently increased in the pancreas during acute pancreatitis. Moreover, by using genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones, we showed that T3 was required to promote proliferation of pancreatic acinar cells, without affecting the extent of tissue damage or inflammatory infiltration. Finally, upon genetic and pharmacological inactivation of selected signalling pathways, we demonstrated that T3 exerted its mitogenic effect on acinar cells via a tightly controlled action on different molecular effectors, including histone deacetylase, AKT, and TGFβ signalling. In conclusion, our data suggest that local availability of T3 in the pancreas is required to promote acinar cell proliferation and provide the rationale to exploit thyroid hormone signalling to enhance pancreatic regeneration.

This article is protected by copyright. All rights reserved.

KEYWORDS:

T3; acinar proliferation; acute pancreatitis; deiodinases; thyroid hormones

PMID: 30714146

DOI: 10.1002/path.5247

ncbi.nlm.nih.gov/pubmed/307...

[jgelliss]

Thank You helvella . Very Interesting .

[Eton]

Helvella- what does this mean in simple terms? I have a cyst on my pancreas and am concerned about the possibility of this developing into something nasty longer term. I read an article recently about meds for hypothyroidism being linked to increased risk of stomach, pancreatic,, lung and breast cancer.

[helvella Administrator Thyroid UK in reply to Eton]

As far as I understand, it is saying that inadequate T3 availability within the pancreas prevents the pancreas healing itself. So it might be possible, somehow, to use T3 to help in that healing process.

I have no idea whatsoever what effect thyroid hormones have on pancreatic cysts, I'm afraid.

I'd be very wary of claims that thyroid hormones are linked to cancers. There is a huge distinction between something, possibly, being associated with cancer and that something actually causing cancer.